The Origin of Life

What do we know about how it all began? Will we ever know for sure?

Of all the great mysteries of science, the origin of life is maybe the one least likely to ever be solved. It is a singular event that happened four billion years ago in a world vastly different from ours. Scientists have developed a lot of ideas about it and increased knowledge of this original environment, but in the end, despite intense interest, the best we will be able to do is informed speculation. Which is, sure, better than uninformed speculation, (aka theology), but still unsatisfying. 

A recent paper about sugars and early metabolism (and a more fully argued precursor) piqued my interest in this area. It claimed that there are non-enzymatic ways to generate most or all of the core carbohydrates of glycolysis and CO2 fixation around pentose sugars, which are at the core of metabolism and the supply of sugars like ribose that form RNA, ATP, and other key compounds. The general idea is that at the very beginning of life, there were no enzymes and proteins, so our metabolism is patterned on reactions that originally happened naturally, with some kind of kick from environmental energy sources and mineral catalysts, like iron, which was very abundant. 

That is wonderful, but first, we had better define what we mean by life, and figure out what the logical steps are to cross this momentous threshold. Life is any chemical process that can accomplish Darwinian evolution. That is, it replicates in some fashion, and it has to encode those replicated descendants in some way that is subject to mutation and selection. With those two ingredients, we are off to the races. Without them, we are merely complex minerals. Crystals replicate, sometimes quite quickly, but they do not encode descendent crystals in a way that is complex at all- you either get the parent crystal, or you get a mess. This general theory is why the RNA world hypothesis was, and remains, so powerful. 

The RNA world hypothesis is that RNA is likely the first genetic material, before DNA (which is about 200 times more stable) was devised. RNA also has catalytic capabilities, so it could encode in its own structure some of the key mechanisms of life, therefore embodying both of the critical characteristics of life specified above. The fact that some key processes remain catalyzed by RNA today, such as ribosomal synthesis of proteins, spliceosomal re-arrangement of RNAs, and cutting of RNAs by RNAse P, suggest that proteins (as well as DNA) were the Johnny-come-latelies of the chemistry of life, after RNA had, in its lumbering, inefficient way, blazed the trail. 

In this image of the ribosome, RNA is gray, proteins are yellow. The active site is marked with a bright light. Which came first here-
protein or RNA?

But what kind of setting would have been needed for RNA to appear? Was metabolism needed? Does genetics come first, or does metabolism come first? If one means a cyclic system of organic transformations encoded by protein or RNA enzymes, then obviously genetics had to come first. But if one means a mess of organic chemicals that allowed some RNA to be made and provide modest direction to its own chemical fate, and to a few other reactions, then yes, those chemicals had to come first. A great deal of work has been done speculating what kind of peculiar early earth conditions might have been conducive to such chemistries. Hydrothermal vents, with their constant input of energy, and rich environment of metallic catalysts? Clay particles, with their helpful surfaces that can faux-crystalize formation of RNAs? Warm ponds, hot ponds, UV light.... the suggestions are legion. The main thing to realize is that early earth was surely highly diverse, had a lot of energy, and had lots of carbon, with a CO2-rich atmosphere. UV would have created a fair amount of carbon monoxide, which is the feedstock of the Fischer-Tropsch reactions that create complex organic compounds, including lipids, which are critical for formation of cells. Early earth very likely had pockets that could produce abundant complex organic molecules.

Thus early life was surely heterotrophic, taking in organic chemicals that were given by the ambient conditions for free. And before life really got going, there was no competition- there was nothing else to break those chemicals down, so in a sort of chemical pre-Darwinian setting, life could progress very slowly (though RNA has some instability in water, so there are limits). Later, when some of the scarcer chemicals were eaten up by other already-replicating life forms, then the race was on to develop those enzymes, of what we now recognize as metabolism, which could furnish those chemicals out of more common ingredients. Onwards the process then went, hammering out ever more extensive metabolic sequences to take in what was common and make what was precious- those ribose sugars, or nucleoside rings that originally had arrived for free. The first enzymes would have been made of RNA, or metals, or whatever was at hand. It was only much later that proteins, first short, then longer, came on the scene as superior catalysts, extensively assisted by metals, RNAs, vitamins, and other cofactors.

Where did the energy for all this come from? To cross the first threshold, only chemicals (which embodied outside energy cycles) were needed, not energy. Energy requirements accompanied the development of metabolism, as the complex chemicals become scarcer and they needed to be made internally. Only when the problem of making complex organic chemicals from simpler ones presented itself did it also become important to find some separate energy source to do that organic chemistry. Of course, the first complex chemicals absolutely needed were copies of the original RNA molecules. How that process was promoted, through some kind of activated intermediates, remains particularly unclear.

All this happened long before the last universal common ancestor, termed "LUCA", which was already an advanced cell just prior to the split into the archaeal and bacterial lineages, (much later to rejoin to create the most amazing form of life- eukaryotes). There has been quite a bit of analysis of LUCA to attempt to figure out the basic requirements of life, and what happened at the origin. But this ("top-down") approach is not useful. The original form of life was vastly more primitive, and was wholly re-written in countless ways before it became the true bacterial cell, and later still, LUCA. Only the faintest traces remain in our RNA-rich biochemistry. Just think about the complexity of the ribosome as an RNA catalyst, and one can appreciate the ragged nature of the RNA world, which was probably full of similar lumbering catalysts for other processes, each inefficient and absurdly wasteful of resources. But it could reproduce in Darwinian fashion, and thus it could improve. 

Today we find on earth a diversity of environments, from the bizarre mineral-driven hydrothermal vents under the ocean to the hot springs of Yellowstone. The geology of earth is wondrously varied, making it quite possible to credit one or more of the many theories of how complex organic molecules may have become a "soup" somewhere on the early Earth. When that soup produces ribose sugars and the other rudiments of RNA, we have the makings of life. The many other things that have come to characterize it, such as lipid membranes and metabolism of compounds are fundamentally secondary, though critically important for progress beyond that so-pregnant moment. 

• Notes on US history.
• The fascist playbook.
• Chemosynthetic life is doing very well.
• Decimation leads to decline.
• FYI, a discussion of phosphate.
• FYI, a discussion of hypothetical steps toward RNA self-replication.